chr4-122741921-AAAG-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_152618.3(BBS12):βc.34_36delβ(p.Arg12del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 33)
Exomes π: 0.000014 ( 0 hom. )
Consequence
BBS12
NM_152618.3 inframe_deletion
NM_152618.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.37
Genes affected
BBS12 (HGNC:26648): (Bardet-Biedl syndrome 12) The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_152618.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS12 | NM_152618.3 | c.34_36del | p.Arg12del | inframe_deletion | 2/2 | ENST00000314218.8 | |
BBS12 | NM_001178007.2 | c.34_36del | p.Arg12del | inframe_deletion | 3/3 | ||
BBS12 | XM_011531680.3 | c.34_36del | p.Arg12del | inframe_deletion | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS12 | ENST00000314218.8 | c.34_36del | p.Arg12del | inframe_deletion | 2/2 | 1 | NM_152618.3 | P1 | |
BBS12 | ENST00000433287.1 | c.34_36del | p.Arg12del | inframe_deletion | 3/3 | 2 | |||
BBS12 | ENST00000542236.5 | c.34_36del | p.Arg12del | inframe_deletion | 3/3 | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251288Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135814
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461808Hom.: 0 AF XY: 0.0000124 AC XY: 9AN XY: 727204
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74512
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome 12 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 25, 2017 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 31, 2020 | - - |
BBS12-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 20, 2023 | The BBS12 c.34_36delAGA variant is predicted to result in an in-frame deletion (p.Arg12del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0044% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-123663076-AAAG-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2020 | This variant, c.34_36del, results in the deletion of 1 amino acid(s) of the BBS12 protein (p.Arg12del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs752885483, ExAC 0.006%). This variant has not been reported in the literature in individuals with BBS12-related conditions. ClinVar contains an entry for this variant (Variation ID: 444639). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at